Role(s) of the 5-HT2C receptor in the development of maximal dentate activation in the hippocampus of anesthetized rats.
CNS Neurosci Ther. 2014-06-17; 20(7): 651-661
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CNS Neurosci Ther. 2014 Oct;20(10):950. Arcangelo, Benigno [corrected to Benigno,
AIMS: Substantial evidence indicates that 5-HT2C receptors are involved in the
control of neuronal network excitability and in seizure pathophysiology. Here, we
have addressed the relatively unexplored relationship between temporal lobe
epilepsy (TLE), the most frequent type of intractable epilepsy, and 5-HT2CRs.
METHODS: In this study, we investigated this issue using a model of partial
complex (limbic) seizures in urethane-anesthetized rat, based on the phenomenon
of maximal dentate activation (MDA) using 5-HT2C compounds, electrophysiology,
immunohistochemistry, and western blotting techniques.
RESULTS: The 5-HT2C agonists mCPP (1 mg/kg, i.p) and lorcaserin (3 mg/kg, i.p),
but not RO60-0175 (1-3 mg/kg i.p.), were antiepileptogenic reducing the MDA
response duration. The selective 5-HT2C antagonist SB242084 (2 mg/kg, i.p)
unveiled antiepileptogenic effects of RO60-0175 (3 mg/kg, i.p) but did not alter
those induced by mCPP and lorcaserin. Compared with control rats, electrically
stimulated rats showed an increase in glutamic acid decarboxylase levels and a
heterogeneous decrease in 5-HT2CR immunoreactivity in different hippocampal
CONCLUSIONS: In our animal model of TLE, mCPP and lorcaserin were anticonvulsant;
likely acting on receptor subtypes other than 5-HT2C. Epileptogenesis induced
early adaptive changes and reorganization in the 5-HT2CR and GABA systems.
© 2014 John Wiley & Sons Ltd.